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Efficacy of dupilumab in COPD with type 2 inflammation
Chronic obstructive pulmonary disease (COPD) is characterised by reduced lung function and frequent exacerbations, which can worsen symptoms, increasing the risk of further health decline and mortality. Although COPD has long been recognised as involving an amplified innate immune response, recent findings suggest that type two inflammation, present in 20–40% of COPD patients, could be a therapeutic target. The BOREAS trial (N Engl J Med 2023;389:205–14) investigated the efficacy and safety of dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13, in reducing exacerbations and improving lung function in COPD patients with type two inflammation. The phase 3, multicenter, double-blind, placebo-controlled trial enrolled 939 COPD patients with blood eosinophil count of at least 300 per microliter, and a high exacerbation risk despite standard triple therapy. Participants were randomised to receive either 300 mg of dupilumab or placebo biweekly for 52 weeks, alongside their standard inhaled therapies. The primary endpoint was the annualised rate of moderate or severe COPD exacerbations. Dupilumab significantly reduced the annualised rate of moderate or severe exacerbations compared with placebo (0.78 vs 1.10; rate ratio, 0.70; 95% CI, 0.58 to 0.86; p<0.001). Additionally, patients treated with dupilumab showed greater improvements in lung function and quality of life, and experienced less severe respiratory symptoms. These benefits were observed within weeks of treatment initiation and persisted throughout the trial. These findings support the role of interleukin-4 and interleukin-13 in the pathophysiology of this COPD subgroup and suggest that dupilumab may be a valuable addition to current treatment regimens.
The impact of early COPD and asma diagnosis and treatment
Worldwide, up to 5% of adults may have undiagnosed asthma or COPD, with many experiencing symptoms and the majority remaining untreated. Aaron, SD, et al (N Engl J Med 2024;390:2061-2073) used targeted case finding to identify adults in the community with respiratory symptoms with undiagnosed lung disease and then assessed whether early diagnosis and guideline-based treatment could improve health outcomes. This randomised controlled trial enrolled 508 participants allocated to receive either specialised pulmonologist-directed care or usual primary care.The primary outcome was the annualised rate of healthcare utilisation for respiratory illnesses, while secondary outcomes included disease-specific quality of life, symptom burden and lung function. During the 12 month trial period, 232 participants (92%) in the intervention group and 153 participants (60%) in the usual-care group began a new treatment for asthma or COPD. Key findings from the study showed that the intervention group had significantly reduced healthcare utilisation compared with the usual-care group (0.53 vs 1.12 events per person-year; 95% CI, 0.36 to 0.63; p<0.001). Improvements in quality of life and symptom burden were also more pronounced in the intervention group. Additionally, the FEV1 increased by 119 mL in the intervention group, compared with 22 mL in the usual-care group underscoring the importance of early treatment in preserving lung capacity and preventing disease progression. This study underscores the value of early detection and specialist intervention in improving clinical outcomes for patients with COPD and asthma. Healthcare providers should consider adopting proactive case-finding approaches and integrating specialist care with regular training sessions and interactive discussions to enhance the management of these chronic respiratory diseases.
Boosting exercise with high-intensity NIV in severe COPD: a game changer?
Patients with very severe COPD and chronic hypercapnic respiratory failure often experience significant dyspnoea and reduced exercise capacity during exercise training. Schneeberger et al (BMJ Open Respir Res. 2023;101:e001913) studied the effects of non-invasive ventilation (NIV) during cycle exercise within a 3 week pulmonary rehabilitation programme in COPD patients with chronic hypercapnia on nocturnal NIV. This randomised controlled trial included 26 participants allocated to exercise training either with high-intensity NIV (HI-NIV) or without NIV. In the HI-NIV group, nocturnal NIV settings were adjusted to provide a more robust ventilation to enhance respiratory muscle rest and normalise PaCO2 levels. The primary outcome was the change in cycle endurance time. Secondary outcomes included dyspnoea, physiological measures, and quality of life indicators. Both groups showed significant improvements in cycle endurance (HI-NIV: +246 s, control: +141 s), but there was no significant between-group difference (95% CI (−92 to 302), p=0.608). The HI-NIV group reported significantly less dyspnoea during exercise training and at isotime during the post-pulmonary rehabilitation cycle endurance test. Most participants in the HI-NIV group expressed a preference for continuing exercise training with NIV. The reduction in dyspnoea highlights the potential for HI-NIV to enhance exercise comfort and tolerance encouraging sustained participation in pulmonary rehabilitation programmes.
Optimizing oxygen delivery in COPD patients
During exercise, oxygen can delay muscle fatigue, reduce dyspnoea and improve exercise endurance in COPD patients. Maintaining adequate oxygen saturations (SpO2) with varying metabolic demands during exercise and physical activity is difficult with constant flow oxygen systems (CFOS). To overcome this challenge, an automatically titrating oxygen system (ATOS), which regulates oxygen flow to maintain a predefined SpO2-target, has been proposed as a solution to optimise the effects of oxygen therapy. Schneeberger et al (Thorax 2023;78:326–334) aimed to compare the efficacy of ATOS vs titrated CFOS on walking capacity in COPD patients with hypoxaemia. This randomised controlled, double-blind, crossover trial included 50 COPD patients (GOLD stage III to IV). Participants performed two endurance shuttle walk tests (ESWTs): one with individually titrated CFOS and one with ATOS targeting an SpO2 of 92%. The primary outcome was walking time. ATOS significantly increased walking time compared with CFOS (median difference+144.5 s, p<0.001). At isotime, SpO2 was significantly higher with ATOS (+3%, p<0.001), while transcutaneous carbon dioxide levels, respiratory rate, and heart rate were comparable. End-exercise partial pressure of oxygen (+8.85 mm Hg) and dyspnoea (−0.5 points) significantly favoured ATOS (both p<0.001). These findings underscore the substantial improvement in walking endurance achieved with automatically titrating systems, which could enhance patient outcomes during pulmonary rehabilitation and provide a promising approach to personalised oxygen therapy.
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Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.